02 September 2019

Instead of analgesics

CRISPR makes it possible to save a person from pain

Yekaterina_t, Madrobots company blog, Habr

For several years CRISPR has been faithfully serving geneticists who, with the help of this technology, have been able to reach new heights in editing the animal genome and studying human DNA. Now scientists are developing a new technology that, apparently, will be able to turn off pain in those who need it.

People who do not feel pain are very rare, they were known about long before the beginning of the XXI century. As it turned out, they have a certain mutation that blocks the gene responsible for pain. In particular, such a gene was absent from a traveling artist from Pakistan – a boy who performed on the streets with amazing numbers. He plunged knives into his palms and walked on hot coals without the slightest signs of pain. 

Despite the fact that his limbs were damaged, the boy continued to perform – he deliberately did not cause particularly large damage to his body. This continued until he was 14 years old. Someone persuaded the artist to jump from the roof as a demonstration of his skill. He agreed, because he knew it wouldn't hurt. It probably didn't hurt, but the boy died when he fell. Subsequently, scientists were able to study his body and DNA. 

By the way, the boy was not deprived of touch and other senses. He felt cold and warm, the texture of objects. Actually, he was no different from all other people, except for a complete lack of sensitivity to pain. Experts published an article on the study of this feature in 2006. 

Now scientists are using CRISPR to develop a technology that can relieve people from pain. Of course, not everyone, because pain is a very useful mechanism acquired as a result of millions of years of continuous evolution of multicellular organisms. No, we are talking about those who need relief from pain – cancer patients, diabetics, people with chronic pain syndrome acquired after injury, as well as patients with other problems. This genetic tool will become an alternative to opioids. 

And we are not talking about a theory or a project that is planned to be implemented in the distant future. Specialists from the University of California have already demonstrated the possibilities of their development on mice. The study was led by Ana Moreno, CEO of the startup Navega Therapeutics.

Pain blocking using the new technology is not done forever, the pain is blocked for a certain time. Using CRISPR, scientists have learned to turn off the key molecule in the spinal cord, which causes pain. The results of the study have already been published on the bioRxiv website (Moreno et al., Long-lasting Analgesia via Targeted in vivo Epigenetic Repression of Nav1.7). 

The testing of CRISPR to work with the human genome was carried out quite recently. So, this year CRISPR Therapeutics tested a tool for the treatment of sickle cell anemia. Another company, Editas Medicine, plans to use the same tool to treat hereditary blindness. Both projects involve changing the human genome to "correct" a certain section of DNA.

If pain blocking technology is created and approved for use in hospitals, it will become very popular. The fact is that up to 20% of people suffer from chronic pain of one kind or another – in any case, this is exactly the statistics in the USA.

As for the "pain gene", scientists believe that it is SCN9A. In the nervous system, namely in the sodium channel NaV1.7, its protein plays the role of a "pain carrier" that transmits specialized signals to the brain. It is worth noting that the Pakistani boy did not have the SCN9A gene, but in some cases the mutation of this DNA site leads to increased pain. I.e., all other things being equal, a person with a specific SCN9A mutation will feel pain more than any of us. 

Now the search for a "cure for pain" is conducted by different companies. Some are trying to develop pharmaceuticals that will block pain. In particular, Voyager Therapeutics and Coda Biotherapeutics are engaged in such developments. But it seems that luck smiled only on scientists from the University of California. Experiments conducted on mice have shown that animals do not feel pain, but heat and cold, as in the case of a Pakistani boy, yes. 

Disabling pain is possible only in the most critical cases. So, the relatives of the deceased boy suffered from fractures of limbs and fingers, which they did not feel. Some people bit off parts of their tongue while eating, without realizing it. But, as mentioned above, in some cases the pain needs to be turned off, because there is simply no way out. 

So far, this is an expensive pleasure – the authors of the development believe that at this stage "pain treatment" will cost a couple of million US dollars. 

Of course, the military is also interested in relieving people from pain – as a creation of super-soldiers. Previously, such opportunities were demonstrated only in science fiction films, but now, it seems, fantasies are becoming reality.

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